1. Field of the Invention
The present invention relates to new thiazolidine derivatives possessing very strong an anti-amnestic activity, a process for preparing same and an anti-amnestic composition containing at least one of the thiazolidine derivatives together with a conventional excipient. More particularly, the present invention relates to 3-(N-benzyloxycarbonyl)-prolyl- or -thioprolyl-4-formyl or hydroxymethyl-thiazolidine, a process for preparing same by reacting 4-benzyloxycarbonyl-proline or -thioproline with thioprolinol and, if necessary, oxidizing the resultant 4-hydroxymethyl-thiazolidine compound to the corresponding 4-formyl-thiazolidine compound, and an anti-amnestic composition containing the thiazolidine compound together with a conventional excipient. As 4-hydroxymethyl and 4-formyl thiazolidines are derived from proline by reduction and are called thioprolinol and thioprolinal, respectively, the nomenclatures of prolinol and prolinal will be used hereinafter for mentioning the compound names concretely in place of the corresponding thiazolidine compounds. However, the compounds of this invention are generally designated herein as the thiazolidine derivatives.
2. Description of the Prior Art
In recent years, some prolinal derivatives are reported as having an inhibitory activity to a physiological role of an enzyme in neuropeptide metabolism. For example, T.C. Friedman et al. reported in J. Neurochem. 42, 237(1984) that N-benzyloxycarbonyl-L-prolyl-L-prolinal (Z-pro-prolinal) exhibited in vivo an inhibitory activity to prolyl endopeptidase. In M. Nanri et al., Folia Pharmacol. japon, 89, 323-329(1987) and K. Taira et al., ibid. 89, 243-252, there is described that some prolinal derivatives exhibit an inhibitory activity to prolyl endopeptidase in experiments using mice as test animal and the use of these derivatives has possibility for the remedy of senile dementia. A similar report is seen in T. Yoshimoto et al., J. Pharmaco bio-Dyn., 10, 730-735(1987). Further, Japanese Laid-open Patent Appln. No. Sho. 60-172929 discloses that Z-glycyl-L-prolyl-chloromethane or -diazomethane has an inhibitory activity to prolyl endopeptidase and is utilizable as anti-amnestic agent. In Japanese Laid-open Patent Appln. No. Sho. 60-188317, there is disclosed that a prolinal which is N-substituted by an amino acid has an inhibitory activity to prolyl endopeptidase and can thus be used as an anti-amnestic agent. Furthermore, Japanese Laid-open Patent Appln. No. Sho. 62-270557 discloses a new process for preparing Z-proprolinal. However, the inhibitory activity to prolyl endopeptidase of these prolinal derivatives is still unsatisfactory in practical level, and so there is a great demand to develop new compounds which exhibit a very strong inhibitory activity to prolyl endopeptidase.